Associations of MC4R, LEP, and LEPR Polymorphisms with Obesity-Related Parameters in Childhood and Adulthood

Abstract

MC4R, LEP, and LEPR genes are involved in the hypothalamic leptin-melanocortin regulation pathway, which is important for energy homeostasis. Our study aimed to evaluate the associations between the MC4R rs17782313, LEP rs7799039, and LEPR rs1137101 polymorphisms with obesity-related parameters in childhood and adulthood. The data were obtained from the Kaunas Cardiovascular Risk Cohort study, which started in 1977 with 1082 participants aged 12–13 years. In 2012–2014, the follow-up survey was carried out. Genotype analysis of all respondents (n = 509) aged 48–49 years was performed for the gene polymorphisms using Real-Time Polymerase Chain Reaction. Anthropometric measurements were performed in childhood and adulthood. In childhood, only skinfold thicknesses were associated with gene variants being the lowest in children with MC4R TT genotype and LEP AG genotype. In adulthood, odds of obesity and metabolic syndrome was higher in MC4R CT/CC genotype than TT genotype carriers (OR 1.8; 95% CI 1.2–2.8 and OR 1.6; 95% CI 1.1–2.4, respectively). In men, physical activity attenuated the effect of the MC4R rs17782313 on obesity. The LEP GG genotype was associated with higher BMI, waist circumference, and visceral fat level only in men. No associations of the LEPR rs1137101 polymorphisms with anthropometric measurements and leptin level were found. In conclusion, the associations of the MC4R and LEP gene polymorphisms with obesity-related parameters strengthened with age.

Cardiorespiratory Fitness and Muscular Strength Moderates the Relationship between FNDC5 Polymorphism and Adiposity in Children and Adolescents

“…However, it must be considered that the prevention and treatment of childhood obesity is a complex task. Additionally, it is known that this disease is of polygenic origin, and other genes are also associated with it, including MCR4 , LEP , FTO, and TMEM18 [ 14 , 32 ]. Knowing that increasing levels of physical activity is an important part of the process, we should mention mechanisms for promoting a more active lifestyle.…”

Correlations of Gene Variants LEP <i>rs2167270</i>, LEPR <i>rs1137100</i>, GHRL <i>rs696217</i>, <i>rs27647</i>, and NPY <i>rs16147</i> with Obesity and Adolescent Eating Behavior: Case-Control Study

“…Исследования ассоциации полиморфных вариантов генов лептина и лептинового рецептора с риском развития ожирения в основном проводились с участием взрослых, и их результаты противоречивы [27]. В России ассоциацию вариантов гена рецептора лептина с развитием детского ожирения у девочек изучали К.Д.…”

The Role of Molecular and Hormonal Factors in Obesity and the Effects of Physical Activity in Children

“…The results of a follow-up study involving 1082 participants aged 12–13 years showed that skinfold thickness was associated with gene variants being lower in children with the MC4R TT genotype and the LEP AG genotype, but no associations were found with BMI [ 132 ].…”